[Identification of a novel NOTCH3 mutation in a family featuring cerebral autosomal dominant arteriopathy with subcortical infarct and leucoencephalopathy].
Zhonghua Yi Xue Yi Chuan Xue Za Zhi
; 31(5): 578-81, 2014 Oct.
Article
in Zh
| MEDLINE
| ID: mdl-25297585
ABSTRACT
OBJECTIVE:
To analyze potential mutations of NOTCH3 gene in a Chinese family featuring cerebral autosomal dominant arteriopathy with subcortical infarct and leucoencephalopathy (CADASIL) in order to facilitate genetic counseling and prenatal diagnosis.METHODS:
The proband and related family members and 100 healthy controls were recruited. The NOTCH3 gene was screened for mutations by polymerase chain reaction and direct DNA sequencing. PolyPhen-2 and SIFT software were used to predict the protein function.RESULTS:
The proband and two affected individuals from the family were adult-onset, with main clinical manifestations including recurrent transient ischemic attacks and(or) strokes, cognitive impairment, memory decline, and depression. MRI findings suggested multiple cerebral infarcts and severe leukoencephalopathy. A novel heterozygous missense mutation c.3043T> A (p.Cys1015Ser) located in exon 19 of NOTCH3 gene was identified not only in the proband and two patients, but also in an asymptomatic relative from the family. The same mutation was detected in none of the 100 unrelated healthy controls. Function analysis suggested that this mutation can severely affect the functions of this protein. Multiple sequence alignment revealed that the mutation site was extremely conserved in various species.CONCLUSION:
A novel heterozygous Cys1015Ser mutations in exon 19 of the NOTCH3 gene probably underlies the CADASIL in this family.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Exons
/
Mutation, Missense
/
CADASIL
/
Receptors, Notch
Type of study:
Diagnostic_studies
/
Prognostic_studies
Limits:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Language:
Zh
Journal:
Zhonghua Yi Xue Yi Chuan Xue Za Zhi
Journal subject:
GENETICA MEDICA
Year:
2014
Type:
Article